Inflammation occurs as part of a tissue's local response to pathogen invasion, injury or other irritation. The immune response to such injurious conditions is characterized by, both, physiological and cellular/molecular defensive processes of recognizing and destroying invasion or injury.
In the physiological process, blood vessels in the affected region become dilated and capillary permeability becomes increased. This inflammatory response allows for increased blood flow to an affected region and for specialized hematopoietic and mobile tissue cells to be quickly and abundantly dispatched to their site of action.
The cellular response includes the recruitment of various specialized cells of the body's immune system to destroy or otherwise neutralize an offending or injurious agent.
There are generally two stages associated with inflammation—namely “acute” and “chronic” stages. The early stage is termed the acute stage and is the body's initial response to a tissue irritation. If such irritation persists, the immune response enters into the chronic stage. There are specialized white blood cells that tend to be at elevated levels in the acute stage and different ones that tend to exist at elevated levels in the chronic stage.
Lung tissue is susceptible to inflammation, but because of physical constraints, it is extremely difficult to detect. One possible method of detection is through a bronchoscope examination, whereby a clinician may detect inflammation based on visual inspection. Such visual inspection is uncomfortable and intrusive and it suffers from poor sensitivity.
One well-known modality employed to assess acute and chronic pulmonary inflammation is sputum cytology. In this modality, a sample of sputum (produced in the lungs and in the airways leading thereto) is examined under a microscope to determine whether or not inflammatory cells are present. Sputum cytology, however, suffers from numerous shortcomings as described below.
The normal cellular elements in the distal pulmonary tree, bronchioles and alveoli, are columnar ciliated epithelium, nonciliated epithelium (Clara cells), flat epithelial type 1 pneumocytes, goblet cells, and endocrine argentaffin cells. Mobile cells from the blood and interstitial space are also present. These consist of polymorphonuclear leukocytes, lymphocytes, plasma cells, eosinophils, mast cells and macrophages.
Pulmonary inflammation is characterized by an alteration in the number and proportion of the mobile cells. The current microscopic method for assessing inflammation is based on a pathologist's qualitative interpretation of the sputum cytology specimen. By inspecting the slide, the pathologist forms an impression as to what cells lines are present and whether they are increased/normal/decreased in number on an absolute basis, and whether they are increased/normal/decreased in relation to the other cellular constituents.
This type of perceptual analysis—difficult in any situation—is rendered more difficult in the specific circumstances of sputum cytology. Firstly, the cell types are not uniformly dispersed. There are always areas of increased density and other areas of paucity of each cell line. This is the result of the cells not being maintained in a uniform suspension. They are preserved in a substrate, mucus-containing sputum, composed of many non-cellular elements, such as fibrin. Groups of cells may be attracted to the substrate, others repelled. Some groups may be physically entrapped. This confusing scenario, not observed in toto but rather field by field, is not amenable to meaningful or reproducible evaluation. In a recent study, Asthma Research Group, Dept of Medicine, St. Joseph's Hospital and McMaster University, Hamilton, Ontario, CANADA, the authors examined the extent of agreement between clinical judgment of sputum cell counts and actual counts in asthmatic patients (Cohen's Kappa) and the possible predictors of agreement (multiple logistic regression). Sixty-seven of the 76 sputum samples were suitable for analysis. Agreement between expected and actual cell counts occurred in 30/67 patients. The overall agreement for the different cell types was poor (estimated K=0.14, 95% confidence interval (CI)=0.02, 0.26). (Parameswaran et al, 2000).
Another shortcoming of the current microscopic analysis derives from its lack of quantification. The subjective nature of the diagnosis does not allow for comparison of progression or regression over time. Once the diagnosis of pulmonary inflammation is established, it is important to follow the progress of the disease and its response to therapy. A qualitative microscopic diagnosis limits the ability to accomplish this important objective.